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Background: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1-predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has recently been challenged, and Cbl-b overexpression may emerge as an important factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been identified as Th1-Th2 modulators in inflammatory skin diseases, most notably psoriasis, but their roles in leprosy have not yet been elucidated. The occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal elimination of mycobacteria in LL patients, which could theoretically be a portal for contact transmission, thus raises important immunological questions: Do Th17 and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set systemically or locally? Furthermore, which microRNAs (miRs), signal transducers, and activators of transcription (STAT) proteins regulate this transition in leprosy, if any, and does differential Cb1-b expression play a role?, Observation: A 71-year-old man presented with an infiltrative dermopathy characteristic of LL, as well as several hyperkeratotic plaques. Microscopic examination of the hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and transepidermal elimination of acid-fast bacilli, whereas classic histopathologic features of LL were present at other sites., Hypotheses: We hypothesize that: Th17 and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions, manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in LL lesions with PEH, given their association with epithelial hyperproliferation; and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions., Conclusion: By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to recognize these dynamic immunologic processes clinically and histopathologically and devise specific immunologic interventions.

A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer's disease in APOE ε3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, in cognitively intact elderly subjects. APOE ε4 carriers showed significant reductions in Aβ 1-42 levels compared to non-ε4 carriers, but no differences were detected across TOMM40 variants. Neither Aβ 1-40 nor tau levels were affected by APOE or TOMM40.

The ability to utilize serum or plasma samples interchangeably is useful for tuberculosis (TB) serology. We demonstrate a strong correlation between antibody titers to several mycobacterial antigens in serum versus plasma from HIV-infected and non-HIV-infected TB and non-TB patients (r = 0.99 to 0.89; P < 0.0001). Plasma and serum can be used interchangeably in the same antibody detection assays.

A 35-year-old man with severe eczematous dermatitis and recurrent staphylococcal skin infections, some of which required hospitalization, is presented. Other medical concerns include recurrent oral staphylococcal infections, otitis media, ocular herpes simplex virus keratitis, asthma, steroid-induced gastritis, steroid-induced cataracts, recurrent upper respiratory infections, and acute pharyngitis. Past medical history includes retained dentition of six primary teeth, two episodes of childhood pneumonia that required hospitalization, and three wrist and ankle fractures. Laboratory data showed an eosinophil count of 2,400 cells/ml; the highest IgE level was 17,028 IU/mL. Considering the clinical and laboratory findings, the diagnosis of hyperimmunoglobulin E syndrome was made. DNA sequencing showed a novel signal transducer and activator of transcription 3 (STAT3) gene mutation within intron 12, specifically adenine to cytosine, two base pairs upstream of exon 13.

Hermansky-Pudlak syndrome (HPS) is one of the few genetic disorders associated with severe pulmonary fibrosis. Fifty percent of affected patients die as a result of respiratory insufficiency. Fibrosis is thought to be caused by the accumulation of ceroid, an insoluble fluorescent lipoprotein, both extracellularly and in the lysosomes of alveolar macrophages. In addition to pulmonary fibrosis, HPS is characterized by oculocutaneous albinism and a reduction in the number of platelet dense bodies. CD63 is a protein that was described originally in platelet lysosomes. It localizes to the membranes of melanosomes and platelet dense bodies. CD63 is decreased dramatically in the lysosomes and dense bodies of patients with HPS. We theorized that CD63, a membrane protein common to lysosomes, melanosomes, and platelet dense bodies, may play a role in HPS. We sought to characterize the gene coding for this protein in HPS lymphoid cell lines. The coding region for CD63 was sequenced in control and HPS cell lines. Messenger RNA from HPS and normal cell lines was examined by Northern analysis. Genomic DNA from the same cell lines was examined by Southern analysis and polymerase chain reaction (PCR). CD63 protein in lymphoid cell lines and peripheral blood monocytes was compared by Western analysis. We found no mutations in the coding region of CD63 in an HPS cell line. We also found no diminution in the quantity of CD63 RNA by Northern analysis and no gross defects in the structural gene by PCR and Southern analysis, suggesting that the CD63 structural gene, promoter, and untranslated regions were normal. Western analysis showed that the 43-kDa protein was present in control and HPS lymphoid cell lines and peripheral blood monocytes in equivalent amounts. Although CD63 is an attractive candidate for the primary defect of HPS, the disease is probably not caused by a mutation in the CD63 gene.

The pathogenesis of emphysema is considered to be an imbalance of protease and antiprotease activity in the lower respiratory tract leading to uninhibited degradation of lung interstitium by elastolytic enzymes. An increased amount of the serine protease neutrophil elastase (NE) is though to play a major role in this degradation. Because the expression of NE is limited to neutrophil precursors in the bone marrow, we hypothesized that nicotine, which is readily absorbed from lung and distributed to tissue, including bone marrow, would increase expression of the NE gene and protein. HL-60 cells, a myeloblast/promyelocyte cell line, were cultured in the presence or absence of 0.06 and 0.8 microM nicotine for 5 d. Both concentrations of nicotine caused a 2.4- to 3.3-fold increase, respectively, in NE gene expression over unstimulated cells, and NE protein increased 4.8- to 3.4-fold over unstimulated cells, respectively, similar to our positive control DMSO. Nicotine did not induce upregulation of the NE gene by initiating cell differentiation. Both low and high nicotine concentrations upregulate the NE gene in HL-60 cells leading to increased NE protein concentration per cell suggesting a pathophysiologic mechanism for emphysema.